Stuerzebecher et al., Thrombosis Research, vol. 9, 637-646 (1976) describes comparative studies of a number of benzamidine derivatives as Factor Xa inhibitors. The most active inhibitors were 3-amidino-phenylaryl derivatives.
Tidwell et al., Thrombosis Research, vol. 19, 339-349 (1980) describes Factor Xa inhibitory activity of a series of heterocyclic aromatic mono- and di-amidines.
Stuerzebecher et al., Thrombosis Research, vol. 17, 545-548 (1980) describes Factor Xa inhibitory activity of a series of a,a'-bis-(4-amidinobenzyl) cycloalkanones, a,a'-bis-(4-aminobenzylidene)- and a,a'-bis-(3-aminobenzylidene) cycloalkanones with 5 to 8-membered rings, the corresponding non-cyclic derivatives, and derivatives containing only one amidino group.
Hauptmann et al., Blood Coagulation and Fibrinolysis, vol. 4, 577-582(1993) and Hauptmann et al., Thromb. Haemostasis, vol. 63(2), 220-223(1990) report testing of several synthetic compounds as Factor Xa inhibitors: Na-tosylglycyl-3-amidinophenylalanine methyl ester; 2,7-bis(4-amidinobenzylidene)-cycloheptanone-(1); Na-tosyl-4-amidinophenylalanine piperidide; Na-naphthylsulphonylglycyl-4-amidinophenylalanine piperidide; 4-methyl-1-N.sup.2 -(methyl-1,2,3,4-tethydro-8-quinolinesulphonyl-L-arginyl-2-piperidine carbonic acid; and D-phenylalanyl-L-propyl-L-arginine chloromethyl ketone.
Nagahara et al., J. Med. Chem., vol. 37, 1200-1207(1994) describes several dibasic (amidinoaryl)propanoic acid derivatives as Factor Xa inhibitors.
Daiichi EPA 0 540 051 A1, published May 5, 1993, discloses aromatic amidine derivatives, including amidino naphthylenes, amidino-indoles, amidino-benzimidazoles, and amidino-benzothiophenes, which have Factor Xa inhibitory activity.
DuPont Merck WO 95/14683 and WO 95/14682, published Jun. 1, 1995, disclose isoxazoles and isoxaolines as antagonists of the platelet glycoprotein IIb/IIIa fibrinogen receptor. The isoxazoles and isoxaolines of WO 95/14683 are represented by the formula: ##STR2## The isoxazolines of WO 95/14682 are represented by the formula: ##STR3##
Copending, commonly assigned U.S. patent application Ser. No. 08/449597, filed May 24, 1995, discloses isoxazoline antagonists of the platelet glycoprotein IIb/IIIa fibrinogen receptor having the formula: ##STR4##
EP 53095 A and other references disclose various di-anilino-pyrazoline as components of photosensitive systems.
EP 438690 and other references disclose various 1-amido-pyrazolines as pesticides, e.g., insecticides, fungicides and acaricides.
To date there have been no isoxazoline, isothiazoline or pyrazoline derivatives described as Factor Xa inhibitors.